New experimental models are proposed to examine the tumor initiation/promotion regimen in relation to the Epstein-Barr virus (EBV). This may allow better understanding of the causative role of EBV in human disorders such as Burkitt's lymphoma, nasopharyngeal carcinoma and the diseases of X-linked lymphoproliferative syndrome. Using our method of EBV receptor-implantation, mouse and human cells of non-B lymphocyte origin are infected with the virus. Depending on the target cell type, full, partial or no expression of the viral cycle is observed. Thus, the primary interaction between EBV and a target cell can not be dissociated in vitro into the cell-transforming (promotion-related) and nontransforming (unrelated to tumorgenicity) pathways. Experiments are designed to test the hypothesis that the EBV-related oncogenic mechanism, in in vitro virus-cell interaction models, may involve a type of promotion, namely, a virally-mediated increase in an intracellular protein(s) that block(s) viral lytic cycle and interfere(s) with cell differentiation, leading to uncontrolled cell proliferation (transformation) and an ultimate selection of neoplastic cells. We will attempt to: 1) determine and compare patterns of the virus-dependent proteins during the primary EBV-lytic cycle and during the virus-mediated cell transformation; 2) isolate and characterize the major protein(s) involved in the regulation of the EBV-target cell interaction (the putative transformation/promotion regulator); 3) perform initiation/promotion experiments in vitro by attempting to experimentally regulate the EBV-target cell interaction. The proposed studies may lead to further elucidation of the EBV-related oncogenic mechanism and the co-factors involved.